The human Oncostatin M (OSM) gene maps to chromosome 22. Human OSM is expressed as a 252aa polypeptide having a 25 aa signal sequence that is secreted into the extracellular space by epithelial and stromal cells. Proteolytic cleavage near the carboxy-terminus of the mature OSM yields the fully active 209 aa form of OSM having two N-linked glycosylation sites. OSM belongs to the IL-6 family of cytokines that includes (IL-6, IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1, ciliary neutotrophic factor (CNTF) and cardiotrophin-like cytokine (CLC)) which share a common receptor subunit, gp130 protein. In humans, OSM signals through receptor heterodimers consisting of gp130 and the LIFRα subunit or gp130 and the OSMRβ subunit. OSM is produced primarily by cells of immune system origin and, because of the widespread distribution of its signaling receptors, it has been associated with a variety of biological activities, including cell growth regulation, neural development and regulation of extracellular matrix composition.
While human OSM uses both the LIFRα and the OSMRβ to signal, the murine homolog signals only through murine OSMRβ. Thus, the murine protein does not represent a functional surrogate for study of some human OSM pathways.
In addition to the understanding the biological functions of OSM, a need in the art exists to improve current toxicological testing strategies through testing of closely related animal species with human or surrogate biologic proteins. As part of the characterization effort, it is critical to demonstrate reactivity of any therapeutic candidates against the orthologous proteins from available toxicology species, such as cynomologous monkey.